We do research in bioinformatics. Broadly, we are interested in large-scale analyses of the rapidly expanding number of genome sequences and macromolecular structures. It is hoped that these will allow us to address a number of overall, statistical questions about proteins, relating to their physical properties, cellular function, and phylogenetic distribution, More specifically, we have two research foci. The first is comparative genomics. We compare genomes in terms of protein folds, biochemical pathways, and patterns of gene expression. We are also developing methods to cluster proteins into fold families and predict structure and function from sequence similarity. The second focus is the analysis of macromolecular geometry. Here we concentrate on the relationship between packing and motions and try to find standardized ways to describe conformational variability. Again the work is performed in a database framework, through comparison of solved structures. We are collaborating with many members of the CSB. We are working with D Engelman (i) on the prediction and identification of membrane proteins, (ii) on surveying membrane protein dimerization motifs, and (iii) on the analysis of packing in membrane proteins. We are working with P Moore and T Steitz on the analysis of packing in RNA structures. We are also working with T Steitz on the analysis of specific macromolecular motions. We are working with L Regan on biophysically characterizing the structurally uncharacterized proteins in eukaryotic genomes.